Salivary carbonic anhydrase II in winged aphid morph facilitates plant infection by viruses.

Aphids are the most common insect vector transmitting hundreds of plant viruses. Aphid wing dimorphism (winged vs. wingless) not only showcases the phenotypic plasticity but also impacts virus transmission; however, the superiority of winged aphids in virus transmission over the wingless morph is not well understood. Here, we show that plant viruses were efficiently transmitted and highly infectious when associated with the winged morph of Myzus persicae and that a salivary protein contributed to this difference. The carbonic anhydrase II (CA-II) gene was identified by RNA-seq of salivary glands to have higher expression in the winged morph. Aphids secreted CA-II into the apoplastic region of plant cells, leading to elevated accumulation of H+. Apoplastic acidification further increased the activities of polygalacturonases, the cell wall homogalacturonan (HG)-modifying enzymes, promoting degradation of demethylesterified HGs. In response to apoplastic acidification, plants accelerated vesicle trafficking to enhance pectin transport and strengthen the cell wall, which also facilitated virus translocation from the endomembrane system to the apoplast. Secretion of a higher quantity of salivary CA-II by winged aphids promoted intercellular vesicle transport in the plant. The higher vesicle trafficking induced by winged aphids enhanced dispersal of virus particles from infected cells to neighboring cells, thus resulting in higher virus infection in plants relative to the wingless morph. These findings imply that the difference in the expression of salivary CA-II between winged and wingless morphs is correlated with the vector role of aphids during the posttransmission infection process, which influences the outcome of plant endurance of virus infection.

TP53 disruptive mutation predicts platinum-based chemotherapy and PD-1/PD-L1 blockade response in urothelial carcinoma.

TP53 mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity of TP53 mutants leads to heterogeneous clinical outcomes. This study aimed to investigate the clinical relevance of specific TP53 mutations in UrCa. In this study, a total of eight cohorts were enrolled, along with matched clinical annotation. TP53 mutations were classified as disruptive and nondisruptive according to the degree of disturbance of p53 protein function and structure. We evaluated the clinical significance of TP53 mutations in our local datasets and publicly available datasets. The co-occurring events of TP53 mutations in UrCa, along with their therapeutic indications, functional effects, and the tumor immune microenvironment, were also investigated. TP53 mutations were identified in 49.7% of the UrCa patients. Within this group, 25.1% of patients carried TP53Disruptive mutations, a genetic alteration correlated with a significantly poorer overall survival (OS) when compared to individuals with TP53Nondisruptive mutations and those with wild-type TP53. Significantly, patients with TP53Disruptive mutations exhibit an increased probability of responding favorably to PD-1/PD-L1 blockade and chemoimmunotherapy. Meanwhile, there was no noteworthy distinction in OS among patients with varying TP53 mutation status who underwent chemotherapy. Samples with TP53Disruptive mutations showed an enriched APOBEC- and POLE-related mutational signature, as well as an elevated tumor mutation burden. The sensitivity to immunotherapy in tumors carrying TP53Disruptive mutation may be attributed to the inflamed tumor microenvironment characterized by increased CD8+T cell infiltration and interferon-gamma signaling activation. In conclusion, UrCa patients with TP53Disruptive mutations have shown reduced survival rates, yet they may respond well to PD-1/PD-L1 blockade therapy and chemoimmunotherapy. By distinguishing specific TP53 mutations, we can improve risk stratification and offer personalized genomics-guided therapy to UrCa patients. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Integration of CD4+ T cells and molecular subtype predicts benefit from PD-L1 blockade in muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is a disease characterized by molecular and clinical heterogeneity, posing challenges in selecting the most appropriate treatment in clinical settings. Considering the significant role of CD4+ T cells, there is an emerging need to integrate CD4+ T cells with molecular subtypes to refine classification. We conducted a comprehensive study involving 895 MIBC patients from four independent cohorts. The Zhongshan Hospital (ZSHS) and The Cancer Genome Atlas (TCGA) cohorts were included to investigate chemotherapeutic response. The IMvigor210 cohort was included to assess the immunotherapeutic response. NCT03179943 was used to evaluate the clinical response to a combination of immune checkpoint blockade (ICB) and chemotherapy. Additionally, we evaluated genomic characteristics and the immune microenvironment to gain deeper insights into the distinctive features of each subtype. We unveiled four immune-molecular subtypes, each exhibiting distinct clinical outcomes and molecular characteristics. These subtypes include luminal CD4+ Thigh, which demonstrated benefits from both immunotherapy and chemotherapy; luminal CD4+ Tlow, characterized by the highest level of fibroblast growth factor receptor 3 (FGFR3) mutation, thus indicating potential responsiveness to FGFR inhibitors; basal CD4+ Thigh, which could benefit from a combination of ICB and chemotherapy; and basal CD4+ Tlow, characterized by an immune suppression microenvironment and likely to benefit from transforming growth factor-ß (TGF-ß) inhibition. This immune-molecular classification offers new possibilities for optimizing therapeutic interventions in MIBC.

Integrating molecular subtype and CD8+ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer.

BACKGROUND: Luminal and Basal are the primary intrinsic subtypes of muscle-invasive bladder cancer (MIBC). The presence of CD8+ T cells infiltration holds significant immunological relevance, potentially influencing the efficacy of antitumor responses. This study aims to synergize the influence of molecular subtypes and CD8+ T cells infiltration in MIBC. METHODS: This study included 889 patients with MIBC from Zhongshan Hospital, The Cancer Genome Atlas, IMvigor210 and NCT03179943 cohorts. We classified the patients into four distinct groups, based on the interplay of molecular subtypes and CD8+ T cells and probed into the clinical implications of these subgroups in MIBC. RESULTS: Among patients with Luminal-CD8+Thigh tumors, the confluence of elevated tumor mutational burden and PD-L1 expression correlated with a heightened potential for positive responses to immunotherapy. In contrast, patients featured by Luminal-CD8+Tlow displayed a proclivity for deriving clinical advantages from innovative targeted interventions. The Basal-CD8+Tlow subgroup exhibited the least favorable three-year overall survival outcome, whereas their Basal-CD8+Thigh counterparts exhibited a heightened responsiveness to chemotherapy. CONCLUSIONS: We emphasized the significant role of immune-molecular subtypes in shaping therapeutic approaches for MIBC. This insight establishes a foundation to refine the process of selecting subtype-specific treatments, thereby advancing personalized interventions for patients.

Status and related factors of professional growth among young nursing talents: a cross-sectional study in China.

BACKGROUND: The shortage of nurses has been a global human resources problem. A good professional growth environment is essential to developing potential nursing students and attracting nurses to join, and it has great significance in reducing nurse turnover. However, nurses' comprehensive perceptions of professional growth have not yet been examined. METHODS: A cluster sampling method was used to conduct a professional growth questionnaire survey on young nursing talents from a large Chinese public tertiary A hospital in March 2022. RESULTS: The score of professional growth among 243 young nursing talents was 57.92 ± 9.607, with a scoring rate of 77.23%. The scores for dimensions of professional growth, from lowest to highest, were rehabilitation growth, promotion speed, professional goal progress, and professional ability development. Attitudes towards participating in training, service as the quality manager or clinical teacher, self-efficacy, professional title, work-family support, education, and organizational commitment of young nursing talents were significantly associated with professional growth. CONCLUSION: The professional growth of young nursing talents was at a moderate level and needed to be strengthened. Nursing leaders and managers are expected to develop management practices to enhance young nursing talents' professional growth in combination with the related factors.

All Cubic-Phase δ-TAGS Thermoelectrics Over the Entire Mid-Temperature Range.

GeTe-based pseudo-binary (GeTe)x (AgSbTe2 )100- x (TAGS-x) is recognized as a promising p-type mid-temperature thermoelectric material with outstanding thermoelectric performance; nevertheless, its intrinsic structural transition and metastable microstructure (due to Ag/Sb/Ge localization) restrict the long-time application of TAGS-x in practical thermoelectric devices. In this work, a series of non-stoichiometric (GeTe)x (Ag1- δ Sb1+ δ Te2+ δ )100- x (x = 85∼50; δ = ≈0.20-0.23), referred to as δ-TAGS-x, with all cubic phase over the entire testing temperature range (300-773 K), is synthesized. Through optimization of crystal symmetry and microstructure, a state-of-the-art ZTmax of 1.86 at 673 K and average ZTavg of 1.43 at ≈323-773 K are realized in δ-TAGS-75 (δ = 0.21), which is the highest value among all reported cubic-phase GeTe-based thermoelectric systems so far. As compared with stoichiometric TAGS-x, the remarkable thermoelectric achieved in cubic δ-TAGS-x can be attributed to the alleviation of highly (electrical and thermal) resistive grain boundary Ag8 GeTe6 phase. Moreover, δ-TAGS-x exhibits much better mechanical properties than stoichiometric TAGS-x, together with the outstanding thermoelectric performance, leading to a robust single-leg thermoelectric module with ηmax of ≈10.2% and Pmax of ≈0.191 W. The finding in this work indicates the great application potential of non-stoichiometric δ-TAGS-x in the field of mid-temperature waste heat harvesting.

The importance of and difficulties involved in creating molecular probes for a carbon monoxide gasotransmitter.

As one of the triumvirate of recognized gasotransmitter molecules, namely NO, H2S, and CO, the physiological effects of CO and its potential as a biomarker have been widely investigated, garnering particular attention due to its reported hypotensive, anti-inflammatory, and cytoprotective properties, making it a promising therapeutic agent. However, the development of CO molecular probes has remained relatively stagnant in comparison with the fluorescent probes for NO and H2S, owing to its inert molecular state under physiological conditions. In this review, starting from elucidating the definition and significance of CO as a gasotransmitter, the imperative for the advancement of CO probes, especially fluorescent probes, is expounded. Subsequently, the current state of development of CO probe methodologies is comprehensively reviewed, with an overview of the challenges and prospects in this burgeoning field of research.

Charge transport in highly acidic glass-forming protic ionic liquids tailored by zwitterionic precursors.

Highly acidic protic ionic liquids (PILs) are promising materials for potential electrochemical applications due to their high proton conductivity and excellent thermal stability. Still, little is known about the correlation between charge transport and structural dynamics as well as the proton transport mechanism despite the large body of literature on this topic. Here, we have examined the charge transport and structural dynamics by employing broadband dielectric spectroscopy in two highly acidic PILs in their supercooled liquid and glassy states, which included the same anion [TfO]- and different cations, [Tau]+ vs [Ahs]+. Unlike many other ionic liquids, the conductivity relaxation time τe of two studied PILs is substantially faster than the structural relaxation time τα. The decoupling behavior between charge transport and structural dynamics of two materials, which is manifested by a decoupling index Rτ, varies between 0.3 and 2.3 over the temperature range above Tg. Moreover, "Walden" plots of the molar conductivity vs the viscosity qualify both compounds as "Super ILs." All findings support the physical picture of large, polar, and orientationally correlated ion clusters, where the slow α-relaxation can be identified as structural relaxation associated with cooperative reorientations of the cluster macrodipole. In contrast, the shortest timescale for diffusive charge transport, τe, is 1-2 decades shorter than τα, implying that proton hopping is triggered by "single particle" (ions or ion pair) rotations and jumps on a sub-length scale of the cluster size, a dynamics being present even in the glassy state as indicated by a strong ß-relaxation. These results demonstrate the practicality of employing highly acidic PILs in electrochemical fields.

Revisiting Fur Regulon Leads to a Comprehensive Understanding of Iron and Fur Regulation.

Iron is an essential element because it functions as a cofactor of many enzymes, but excess iron causes cell damage. Iron hemostasis in Escherichia coli was transcriptionally maintained by the ferric uptake regulator (Fur). Despite having been studied extensively, the comprehensive physiological roles and mechanisms of Fur-coordinated iron metabolism still remain obscure. In this work, by integrating a high-resolution transcriptomic study of the Fur wild-type and knockout Escherichia coli K-12 strains in the presence or absence of iron with high-throughput ChIP-seq assay and physiological studies, we revisited the regulatory roles of iron and Fur systematically and discovered several intriguing features of Fur regulation. The size of the Fur regulon was expanded greatly, and significant discrepancies were observed to exist between the regulations of Fur on the genes under its direct repression and activation. Fur showed stronger binding strength to the genes under its repression, and genes that were repressed by Fur were more sensitive to Fur and iron regulation as compared to the genes that were activated by Fur. Finally, we found that Fur linked iron metabolism to many essential processes, and the systemic regulations of Fur on carbon metabolism, respiration, and motility were further validated or discussed. These results highlight how Fur and Fur-controlled iron metabolism affect many cellular processes in a systematic way.

The role of organic and inorganic substituents of roxarsone determines its binding behavior and mechanisms onto nano-ferrihydrite colloidal particles.

The retention and fate of Roxarsone (ROX) onto typical reactive soil minerals were crucial for evaluating its potential environmental risk. However, the behavior and molecular-level reaction mechanism of ROX and its substituents with iron (hydr)oxides remains unclear. Herein, the binding behavior of ROX on ferrihydrite (Fh) was investigated through batch experiments and in-situ ATR-FTIR techniques. Our results demonstrated that Fh is an effective geo-sorbent for the retention of ROX. The pseudo-second-order kinetic and the Langmuir model successfully described the sorption process. The driving force for the binding of ROX on Fh was ascribed to the chemical adsorption, and the rate-limiting step is simultaneously dominated by intraparticle and film diffusion. Isotherms results revealed that the sorption of ROX onto Fh appeared in uniformly distributed monolayer adsorption sites. The two-dimensional correlation spectroscopy and XPS results implied that the nitro, hydroxyl, and arsenate moiety of ROX molecules have participated in binding ROX onto Fh, signifying that the predominated mechanisms were attributed to the hydrogen bonding and surface complexation. Our results can help to better understand the ROX-mineral interactions at the molecular level and lay the foundation for exploring the degradation, transformation, and remediation technologies of ROX and structural analog pollutants in the environment.

Ex situ Generation of Thiazyl Trifluoride (NSF3 ) as a Gaseous SuFEx Hub.

Sulfur(VI)-fluoride exchange (SuFEx) chemistry, an all-encompassing term for substitution events that replace fluoride at an electrophilic sulfur(VI), enables the rapid and flexible assembly of linkages around a SVI core. Although a myriad of nucleophiles and applications works very well with the SuFEx concept, the electrophile design has remained largely SO2 -based. Here, we introduce S≡N-based fluorosulfur(VI) reagents to the realm of SuFEx chemistry. Thiazyl trifluoride (NSF3 ) gas is shown to serve as an excellent parent compound and SuFEx hub to efficiently synthesize mono- and disubstituted fluorothiazynes in an ex situ generation workflow. Gaseous NSF3 was evolved from commercial reagents in a nearly quantitative fashion at ambient conditions. Moreover, the mono-substituted thiazynes could be extended further as SuFEx handles and be engaged in the synthesis of unsymmetrically disubstituted thiazynes. These results provide valuable insights into the versatility of these understudied sulfur functionalities paving the way for future applications.

A Three-In-One Assembled Nanoparticle Containing Peptide-Radio-Sensitizer Conjugate and TLR7/8 Agonist Can Initiate the Cancer-Immunity Cycle to Trigger Antitumor Immune Response.

Radiotherapy (RT) has been shown to cause immunogenic cell death (ICD) of cancer cells, which promote the release of tumor-associated antigens, and trigger the cancer-immunity cycle (CIC). However, ICD induced by RT usually does not occur in hypoxic tumor cells due to their resistance to radiation. Moreover, RT also induces programmed death ligand 1 (PD-L1) upregulation on tumor cells, which has an inhibitory effect on T lymphocytes. Therefore, therapy based on CIC must selectively target the restricted steps of antitumor immunity. Herein, the authors design a versatile three-in-one assembling nanoparticle that can simultaneously execute these obstacles. The amphiphilic peptide drug conjugate NIA-D1, containing the hydrophobic radio-sensitizer 2-(2-nitroimidazol-1-yl) acetic acid (NIA), a peptide substrate of matrix metalloproteinase-2, and a hydrophilic PD-L1 antagonist D PPA-1, is constructed and co-assembled with hydrophobic Toll-like receptor (TLR) 7/8 agonist R848 to form nanoparticle NIA-D1@R848. The NIA-D1@R848 nanoparticles combined with RT can trigger the apoptosis of tumor cells and initiate the CIC. In the presence of R848, it promotes the maturation of dendritic cells, which together with protein programmed cell death protein 1 (PD-1) and its ligand PD-L1  blockade to relieve T cell suppression, and amplify the antitumor immune cycle. In conclusion, a functionalized three-in-one nanoparticle NIA-D1@R848 is successfully constructed, which can induce strong systemic antitumor immune response.

A predictive clinical-radiomics nomogram for diagnosing of axial spondyloarthritis using MRI and clinical risk factors.

OBJECTIVES: Construct and validate a nomogram model integrating the radiomics features and the clinical risk factors to differentiating axial spondyloarthritis (axSpA) in low back pain patients undergone sacroiliac joint (SIJ)-MRI. METHODS: A total of 638 patients confirmed as axSpA (n = 424) or non-axSpA (n = 214) who were randomly divided into training (n = 447) and validation cohorts (n = 191). Optimal radiomics signatures were constructed from the 3.0 T SIJ-MRI using maximum relevance-minimum redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithm in the training cohort. We also included six clinical risk predictors to build the clinical model. Incorporating the independent clinical factors and Rad-score, a nomogram model was constructed by multivariable logistic regression analysis. The performance of the clinical, Rad-score, and nomogram models were evaluated by ROC analysis, calibration curve and decision curve analysis (DCA). RESULTS: A total of 1316 features were extracted and reduced to 15 features to build the Rad-score. The Rad-score allowed a good discrimination in the training (AUC, 0.82; 95% CI: 0.77, 0.86) and the validation cohort (AUC, 0.82; 95% CI: 0.76, 0.88). The clinical-radiomics nomogram model also showed favourable discrimination in the training (AUC, 0.90; 95% CI: 0.86, 0.93) and the validation cohort (AUC, 0.90; 95% CI: 0.85, 0.94). Calibration curves (P >0.05) and DCA demonstrated the nomogram was useful for axSpA diagnosis in the clinical environment. CONCLUSION: The study proposed a radiomics model was able to separate axSpA and non-axSpA. The clinical-radiomics nomogram can increase the efficacy for differentiating axSpA, which might facilitate clinical decision-making process.

Chemistry of Pentafluorosulfanyl Derivatives and Related Analogs: From Synthesis to Applications.

Pentafluorosulfanyl (SF5 )-containing compounds and corresponding analogs are a highly valuable class of fluorine-containing building blocks owing to their unique properties. The reason for that is the set of peculiar and tremendously beneficial characteristics they can impart on molecules once introduced onto them. Despite this, their application in distinct scientific fields remains modest, given the extremely harsh reaction conditions needed to access such compounds. The recent synthetic approaches via S-F, and C-SF5 bond formation as well as the use of SF5 -containing building blocks embody a "stairway-to-heaven" loophole in the synthesis of otherwise-inaccessible chemical scaffolds only a few years ago. Herein, we report and evaluate the properties of the SF5 group and analogs, by summarizing synthetic methodologies available to access them as well as following applications in material science and medicinal chemistry since 2015.

Melatonin ameliorates cerebral ischemia-reperfusion injury in diabetic mice by enhancing autophagy via the SIRT1-BMAL1 pathway.

Diabetic brains are more vulnerable to ischemia-reperfusion injury. Previous studies have proved that melatonin could protect against cerebral ischemia-reperfusion (CIR) injury in non-diabetic stroke models; however, its roles and the underlying mechanisms against CIR injury in diabetic mice remain unknown. Streptozotocin-induced diabetic mice and high-glucose-cultured HT22 cells were exposed to melatonin, with or without administration of the autophagy inhibitor 3-methyladenine (3-MA) and the specifically silent information regulator 1 (SIRT1) inhibitor EX527, and then subjected to CIR or oxygen-glucose deprivation/reperfusion operation. We found that diabetic mice showed aggravated brain damage, increased apoptosis and oxidative stress, and deficient autophagy following CIR compared with non-diabetic counterparts. Melatonin treatment exhibited improved histological damage, neurological outcomes, and cerebral infarct size. Intriguingly, melatonin markedly increased cell survival, anti-oxidative and anti-apoptosis effects, and significantly enhanced autophagy. However, these effects were largely attenuated by 3-MA or EX527. Additionally, our cellular experiments demonstrated that melatonin increased the SIRT1-BMAL1 pathway-related proteins' expression in a dose-dependent manner. In conclusion, these results indicate that melatonin treatment can protect against CIR-induced brain damage in diabetic mice, which may be achieved by the autophagy enhancement mediated by the SIRT1-BMAL1 pathway.

Study on superconducting Li-Se-H hydrides.

The structures, stabilities and superconducting properties of LiSeHn (n = 4-10) hydrides at 150-300 GPa were studied by the genetic algorithm (GA) and DFT calculation method. Three stable stoichiometries of LiSeH4, LiSeH6 and LiSeH10 were uncovered under high pressure. Four other metastable stoichiometries of LiSeH5, LiSeH7, LiSeH8, and LiSeH9 were also studied. By analyzing the electronic band structure and electronic density of states, C2 LiSeH4, Pmm2 LiSeH6 and C2 LiSeH10 were all found to be metal phases above 150 GPa. Electron-phonon coupling calculations showed that C2 LiSeH4 and Pmm2 LiSeH6 were promising superconductors. The predicted Tc values of C2 LiSeH4 and Pmm2 LiSeH6 were 77 K at 200 GPa and 111 K at 250 GPa, respectively.

Construction of dual active sites for efficient alkaline hydrogen evolution: single-metal-atoms supported on BC2N monolayers.

Electrocatalytic water splitting suffers from sluggish kinetics towards the hydrogen evolution reaction (HER). Balancing the adsorption/desorption ability towards H* and OH* is considered to be an efficient way to enhance the HER efficiency, but it is too hard at one activity site. In this work, the HER activity of the single 3d transition metal atom-anchored BC2N monolayer (M@BC2N, M = Fe, Co, and Ni) was investigated by a density functional theory approach. Our calculation suggests that an efficient dual-active site is formed on M@BC2N towards the HER, i.e., the metal center M as the OH* active site and its adjacent C atoms as the H* active site. The combination of single M atoms with the BC2N monolayer can effectively tune the electronic structure of dual active sites to optimize the adsorption of H* and OH*, resulting in a HER activity sequence of Fe@BC2N < Co@BC2N < Ni@BC2N. Notably, the HER exchange current density of Ni@BC2N reaches up to 0.53 mA cm-2, which is close to the value for commercial Pt/C, suggesting its huge potential in the HER.

Including formal and informal caregivers in the development of Play Intervention for Dementia: a qualitative study.

BACKGROUND: Play Intervention for Dementia is a practice initiative using play to help people living with dementia (PWD) experience engagements, autonomy, and cognitive stimulation. This program was developed under a participatory paradigm, with extensive contribution from formal and informal caregivers. This article describes how caregivers contributed to the practice principles, materials, and assessment during the development phase of Play Intervention for Dementia through community-based participatory research (CBPR). METHODS: Three service supervisors, 16 formal caregivers and 14 informal caregivers from the community participated in this study. Based on CBPR, the study progressed in a reflexive, iterative and collaborative way. Data were collected from diverse sources, including practice journals, observation notes and reflexive focus group interviews. Two trained qualitative researchers conducted thematic analysis on the data collected, with focus on practical skills, outcomes, and caregivers' general experience during the intervention. RESULTS: The therapeutic and liberating power of play was thoroughly discussed by the caregivers. They considered play as an innovative way to understand, engage, and connect with the PWD. Also, improvement in energy level, motivation and communicative capacity was observed among the PWD. The researcher and caregivers collaboratively refined and designed the protocol of Play Intervention for Dementia, adding localized principles and games to the original design. CONCLUSION: Caregivers found play to be a meaningful way to engage with PWD, as it provided an equal platform for them. The intervention also enabled them to reflect upon ageing and disease at a deeper level. Caregivers have contributed significantly to the refinement and contextualisation of the intervention. The efficiency of the refined program should be further tested on a larger scale.

Predictors and prognostic impact of left ventricular ejection fraction trajectories in patients with ST-segment elevation myocardial infarction.

BACKGROUND: There is little evidence on left ventricular ejection fraction (LVEF) trajectories after ST-segment elevation myocardial infarction (STEMI). AIM: We aim to identify the LVEF trajectories after STEMI and explore their predictors and association with prognosis. METHODS: This is a retrospective, observational study of STEMI patients. The LVEF trajectories were identified by the latent class trajectory model in patients with baseline LVEF < 50%. We used logistic regression analysis to investigate the predictors for LVEF trajectories. The Cox proportional hazard model was used to assess the impact of LVEF trajectories on prognosis. The primary outcomes were cardiovascular mortality and heart failure (HF) rehospitalization. RESULTS: 572 of 1179 patients presented with baseline normal LVEF (≥ 50%) and 607 with baseline reduced LVEF (< 50%). Two distinct LVEF trajectories were identified in patients with baseline reduced LVEF: recovered LVEF group and persistently reduced LVEF group. Higher baseline LVEF, lower peak troponin T, non-anterior MI, and lower heart rates were all found to be independently associated with LVEF recovery. After multivariate adjustments, patients with persistently reduced LVEF experienced an increased risk of cardiovascular mortality (HR 7.49, 95% CI 1.94-28.87, P = 0.003) and HF rehospitalization (HR 3.54, 95% CI 1.56-8.06 P = 0.003) compared to patients with baseline normal LVEF. Patients with recovered LVEF, on the other hand, showed no significant risk of cardiovascular mortality and HF rehospitalization. CONCLUSION: Our study indicated two distinct LVEF trajectories after STEMI and that the persistently reduced LVEF trajectory was related to poor prognosis. In addition, several baseline characteristics can predict LVEF recovery.

Distributed Random Beacon for Blockchain Based on Share Recovery Threshold Signature.

Random beacons play a crucial role in blockchains. Most random beacons in a blockchain are performed in a distributed approach to secure the generation of random numbers. However, blockchain nodes are in an open environment and are vulnerable to adversary reboot attacks. After such an attack, the number of members involved in a random number generation decreases. The random numbers generated by the system become insecure. To solve this problem while guaranteeing fast recovery of capabilities, we designed a threshold signature scheme based on share recovery. A bivariate polynomial was generated among the participants in the distributed key generation phase. While preserving the threshold signature key share, it can also help participants who lost their shares to recover. The same threshold setting for signing and recovery guarantees the security of the system. The results of our scheme show that we take an acceptable time overhead in distributed key generation and simultaneously enrich the share recovery functionality for the threshold signature-based random number generation scheme.